Over 20 million people in the United States suffer from degenerative joint diseases. This results in over 2 million arthroscopic surgeries and about 250,000 knee and hip replacements each year. The result is a healthcare burden of over $1 billion dollars every year.
Degenerative joints are treated in the following manner:                Oral non-steroidal anti-inflammatory drugs (NSAIDs).        Visco-supplementation via interarticular hyaluronic acid injections.        Interarticular steroid injection.        Joint replacement.        
This invention is related to visco-supplementation via interarticular injections. Currently all approved therapies of this type are comprised of hyaluronic acid or its sodium salt, commonly referred to as sodium hyaluronate, any one of which is herein referred to as HA. The explanations for the efficacy of HA vary. Some experts believe that HA provides benefits by lubricating the articular joint surfaces. Others believe it provides cushioning. Still others believe it is incorporated directly into the extra-cellular matrix of the synovial space, while still others believe it may provide a target, other than the joint tissues, for the inflammatory agents responsible for joint degeneration.
The flaw in these theories is that study after study has shown that the average residence time of HA injected into the synovial space is only 24 to 48 hours. There is no data to suggest that HA is incorporated into the extra-cellular matrix, and if HA vacates the space in only 24 to 48 hours, none of the other theories previously mentioned can explain the clinical data that HA provides 6 to 12 months of pain reduction. In order for HA to provide this level of benefit, some other mechanism must be at work.
It is theorized herein that the true mechanism behind the efficacy of HA is the poly-anionic nature of the molecule. Inflammatory cytokines, matrix-metallo-proteinases, and other biological molecules that are found in degenerative joints are proteins. Some proteins have a net negative charge, some have a net positive charge and some have a net neutral charge. Regardless of the net charge, all proteins have some portion that is positively charged. HA, on the other hand, is a polysaccharide that is fully negatively charged. Because of this, it is likely that the mechanism of efficacy is the extraction of inflammatory agents from the synovial tissues, electrostatic binding of these agents along the long chain of the HA molecule along its negatively charged carboxylic acid groups, and the subsequent removal of these agents when the HA vacates the synovial space.
If this theory is correct, it stands to reason that a biological polymer with a higher polyanionic charge density (i.e., more negative charges per equal mass of polymer) will be more efficacious at treating degenerative joint diseases than HA.
In order to test the efficacy of PGGA, inflammatory agents in OA were first identified. Various researchers have noted these agents [Sabatini M, Lesur C, Thomas M, Chomel A, Anract P, de Nanteuil G, Pastoureau P., “Effect of inhibition of matrix metalloproteinases on cartilage loss in vitro and in a guinea pig model of osteoarthritis”, Arthritis Rheum. 2005 January; 52(1):171-80]. Of particular interest are the MMPs, and in particular, MMP-1, MMP-8, and MMP-13 which all have collagenase activity. This is because type 2 collagen in the main connective protein in the extra-cellular matrix of the cartilage in the knee and hip. All of these MMPs degrade this collagen, and hence, degrade the matrix and the cartilage.
Of the three MMPs, MMP-13 is the most potent and is selectively expressed in pathological conditions such as arthritis [Pelletier JP, Martel-Pelletier J, Abramson S B., “Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets”, Arthritis Rheum. 2001 June; 44(6):1237-47]. Therefore, it makes sense that if a molecule, such as PGGA, inhibits the activity of MMP-13 it would likely protect the extra-cellular matrix and protect the cartilage. Such a molecule would make for a new and effective treatment for OA.